Agnieszka Z. Balkowiec, M.D. (1993), Ph.D (1995, Med. U. Warsaw). Assistant Professor

Research Interests:  Development and Plasticity of Neuronal Circuits

During nervous system development, differences in levels and patterns of activity among neurons underlie structural rearrangements in neural circuits and selective strengthening of synaptic connections. A fundamental objective of neurobiology, and the long-range objective of my research, is to understand how patterned neuronal activity is translated into changes in synaptic strength. What are the factors that mediate this translation? What are the cellular events and molecular mechanisms that govern activity-dependent functional maturation and plasticity of neural circuits? Are there differences in the mechanisms underlying activity-dependent synaptic modifications between central and peripheral synapses? My research focuses on addressing these and related questions, using two model systems: 1) dissociate cultures of developing hippocampal neurons, and 2) primary and second-order visceral sensory neurons in the arterial baroreceptor pathway.

BDNF and Activity-Dependent Synaptic Development

One line of my current research focuses on the regulation of the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) in hippocampal and primary visceral sensory neurons by physiological patterns of neuronal activity. BDNF is abundantly expressed by these neurons during development and in the adult, and plays a critical role in activity-dependent modulation of synaptic strength and neuronal connectivity. However, mechanisms of BDNF actions, including regulation of BDNF expression, trafficking and release by patterned activity are not understood. We recently demonstrated that the magnitude of native BDNF release from both hippocampal and primary visceral sensory neurons depends on stimulus pattern, indicating that BDNF can encode temporal features of presynaptic neuronal activity. My goal is to dissect the cellular events associated with regulation of native BDNF by physiologically-relevant patterns of stimulation. To achieve this goal, I employ a multidisciplinary approach that includes: a highly sensitive BDNF ELISA in situ, electrical field stimulation, calcium imaging, immunocytochemistry, and pharmacological techniques.

Development of the Arterial Baroreceptor Pathway

Another line of my current research addresses the role of BDNF in functional maturation and plasticity of glutamatergic synapses, using the arterial baroreceptor pathway as a model. The arterial baroreceptors play a critical role in the reflex control of arterial blood pressure. The sensory component of the reflex consists of 1) primary sensory neurons located in the cranial nodose-petrosal ganglion (NPG) complex, and 2) sensory-relay neurons in the brainstem. The sensitivity of the arterial baroreceptor reflex changes during the early postnatal period, and the efficacy of glutamatergic synaptic transmission between baroreceptor afferents and second-order neurons in the brainstem is determined by the frequency of baroreceptor afferent firing. However, mechanisms underlying either functional maturation or frequency-dependent plastic changes at baroreceptor synapses are not well understood. Moreover, diminished baroreceptor reflex leads to increased blood pressure variability, a potentially life-threatening condition in post-infarction patients.

BDNF is highly expressed in the NPG complex, including baroreceptor afferents, and the magnitude of BDNF release from NPG neurons is strongly regulated by the frequency and pattern of neuronal activity. In addition, exogenous BDNF inhibits glutamatergic AMPA currents in second-order neurons that receive sensory information from NPG afferents. Together, these data suggest that BDNF, released from the central terminals of primary sensory neurons, modulates excitatory transmission in visceral sensory pathways, including the arterial baroreceptor pathway. Therefore, this system provides an attractive model for studying both developmental and adult plasticity of synaptic strength within a functional circuit. One of my goals is to define the role of BDNF in regulating activity and expression of glutamatergic AMPA and NMDA receptors in identified second-order neurons in the arterial baroreceptor pathway in vitro and in vivo, using a combination of immunohistochemical, in vivo anterograde tracing and patch-clamp recording techniques. Another goal is to examine the role of BDNF in regulating activity and expression of other transmitter receptors and ion channels involved in synaptic transmission in the arterial baroreceptor pathway. The long-term goal of these studies is to identify cellular and molecular mechanisms responsible for activity-dependent development and plasticity in the arterial baroreceptor pathway that may be relevant to developmental and other disorders of cardiovascular control, such as orthostatic hypotension.

Recent publications:

A.Balkowiec & D.M.Katz (1998). Brain-derived neurotrophic factor is required for normal development of the central respiratory rhythm in mice. Journal of Physiology (London) 510: 527-533.

A.Balkowiec, D.L.Kunze & D.M.Katz (2000). BDNF acutely inhibits AMPA-mediated currents in developing sensory relay neurons. Journal of Neuroscience 20: 1904-1911.

A.Balkowiec & D.M.Katz (2000). Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected by ELISA in situ. Journal of Neuroscience 20: 7417-7423.

A.Balkowiec & D.M.Katz (2002). Cellular mechanisms regulating activity-dependent release of native BDNF from hippocampal neurons. Journal of Neuroscience, 22:10399-10407..

Email Address:  balkowie@ohsu.edu